Composition 1 represents a novel treatment for cocaine overdose and addiction through a mechanism of specific and rapid cocaine hydrolysis. In Composition 1, the N-terminus of human serum albumin (HSA) has been genetically fused to the C-terminus of the catalytic domain of human butyrylcholinesterase (BChE). Residues 1-529 correspond to the catalytic domain of BChE while the sequence of residues 530-1114 is identical to the mature native form of human serum albumin. A few amino acid substitutions have been introduced within the catalytic domain of BChE to improve the cocaine hydrolytic activity of Composition 1, and the terminal tetramerization domain (45 residues of the C-terminus) has been truncated. The HSA moiety of the fusion protein confers an extended half-life (U.S. Publication No. 2011/0312900 A1).
The previous product formulation contains 30 mg/mL of Composition 1 in 10 mM phosphate, 200 mM mannitol, 60 mM trehalose, and 0.01% polysorbate 80 (PS80), pH 7.2 (PMTT) (U.S. Publication No. 2011/0312900 A1).